Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study

Abstract

Background: The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. Objective: We evaluate the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. Methods: A retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with FPC from 2009-2010, followed up until December 31, 2019. We measured the incidence of SPCs per 10,000 person-years and the standardized incidence ratio (SIR) compared to those expected in the general population. Results: Among 266,241 survivors (mean age at FPC, 55.7 years; 56.1% women), we observed 7,348 SPCs during 1,003,008 person-years of follow-up (median, 4.3 years), representing a 26% lower risk of developing SPCs (SIR, 0.74 [95% CI, 0.72-0.76]). Overall, within the men, 14 of the 20 FPC types had significantly lower risk of developing any SPCs, whereas in the women, 7 of the 21 FPC types had significantly lower risk of developing any SPCs. The risk of developing any type of SPC differed by age; the risk was 28% higher in young (< 40 years) cancer survivors (SIR, 1.28 [95% CI, 1.16-1.42]; incidence, 30 per 10,000 person-years), while 27% lower in middle-aged and older (≥ 40 years) cancer survivors (SIR, 0.73 [95% CI, 0.71-0.74]; incidence, 80 per 10,000 person-years) compared with risks in the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung and prostate cancer (21.6% and 15.2%, respectively) in men, and breast and lung cancer (18.9% and 12.2%, respectively) in women. The risk of brain cancer in colo-rectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors was significantly higher in both sexes. Other high-risk SPCs varied according to the type of FPC and sex. Strong positive associations among smoking-related cancers were observed, such as laryngeal, head & neck, lung, and esophageal cancers. Substantial variation existed in the associations of specific types of FPC with specific types of SPC risk, which may be linked to hereditary cancer syndrome; breast cancer survivors for ovarian cancer and colo-rectal cancer survivors for uterus cancers in women, and kidney cancer survivors for pancreas cancer in men. Conclusions: The varying risk of SPCs by age, sex, and the types of FPC in cancer survivors implies the necessity for taiolored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs. © 2023 JMIR Publications Inc.. All rights reserved.